Steric effects at C-20 and C-24 on the metabolism of sterols by Tetrahymena pyriformis.
Cultures of Tetrahymena pyriformis were incubated with various sterols and the extent of dehydrogenation at C-7 and C-22 was determined. The sterols incubated were desmosterol, 22-dehydrodesmosterol, 24-methyldesmosterol, 24 alpha-methylcholesterol (campesterol), 24-methylene-cholesterol, isohalosterol (26,27-bisnorcampesterol, also known as 24,24-dimethylchol-5-en-e beta-ol, a naturally occurring C26-sterol), and 20-isohalosterol. 20-Isohalosterol was not metabolized, while products with delta 7- and delta 22-bonds were formed from isohalosterol and all of the other sterols studied. This confirms an earlier conclusion, based on results with 20-isocholesterol and cholesterol, that inversion of the configuration from 20(R) to 20(S) completely prevents metabolism both in the nucleus and the side chain. On the other hand, changes in the electronics or stereochemistry at C-24 had a direct affect only on metabolism in the side chain. The presence of a methyl group at C-24 reduced the yield of metabolites with a delta 22-bond relative to those with a delta 7-bond producing an accumulation of 7-dehydro metabolite. A double bond at position-24 counteracted this steric effect, presumably by enhancing the rate of dehydrogenation, and a delta 24(28)-bond was more effect than was a delta 24(25)-bond.
D000818:Animals; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D003897:Desmosterol / Q000031:analogs & derivatives / Q000378:metabolism; D008968:Molecular Conformation; D010840:Phytosterols; D013261:Sterols / Q000378:metabolism*; D013769:Tetrahymena pyriformis / Q000378:metabolism*
D010840:Phytosterols; D013261:Sterols; C032248:24-methyldesmosterol; C032247:22-dehydrodesmosterol; D003897:Desmosterol; C032249:halosterol; C021273:campesterol; D002784:Cholesterol; C002537:24-methylenecholesterol